Human Intestinal Microbiome and Surgical Outcomes in Patients Undergoing Colorectal Cancer Surgery

NCT04005118 | Unknown

• 1 other identifier: APHP190088
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Intro: Recent studies on colorectal cancer surgery have been focusing on the role of intestinal microbiome on surgical outcomes. Standard perioperative cares, like mechanic bowel preparation (MBP), administration of antibiotics (ABT) and surgery-related stress and injury influence the microbiome composition and possibly induce a shift toward a microbiome dysbiotic state, which predisposes to complicated postoperative course. Microbiome composition changes and enhanced virulence factors may increase the risk of postoperative complications, such as anastomotic leakage (AL), surgical site infection (SSI), and postoperative ileus (PI), which are known to impact on patient's overall survival and cancer recurrence. Objective: The primary objective is to investigate if a significant association might exist between the microbiome composition and the occurrence of postoperative complications at 90 days. Methods: 3 different microbiome samples will be taken from all patients. Two fresh fecal samples for detection of LM and fecal water preparation: a) a day before the surgery before MBP and/or ABT (LM1), b) postoperatively after first bowel movement (LM2). One sample will be taken intra-operatively from the stapled resection lines of circular stapler used for forming a colorectal anastomosis, to detect the MAM and to perform immunohistochemistry staining for detection of HACE1 expression. DNA analysis will be performed for all samples. IHC will be performed for detecting HACE1 expression in the tumor and colorectal anastomosis tissues using anti-HACE1 antibodies. . For proliferation assessment, human colon carcinoma cell lines HT29 will be plated in monolayers and scratched with a single scratch. Monolayers will be incubated for 24 hours with fecal water from patients with surgical complications and matched control patients without complications. Descriptive statistics will be performed to describe the study population. This project aim to describe microbiome composition and its impact on postoperative complications.

Conditions

Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum

Keywords

Intestinal microbiome; colorectal cancer; mechanical bowel preparation; postoperative complications; anastomotic leakage

Outcome Measures

Primary Outcomes (3)

• Rate of anastomotic leakage

  detected by imaging techiques (CT scan or MRI)

  90 days after surgery

• Rate of surgical site infection

  1)superficial and deep infection:clinical observation of purulent discharge from the wound and/or bacterial staining from the wound 2)organ or deep space infection: imaging techniques (CT, MRI, USS)

  90 days after surgery

• Rate of prolonged postoperative ileuss

  detected by clinical observation of the first bowel movement after the surgery

  90 days after surgery

Secondary Outcomes (7)

• microbiome composition

  3 months after study start date

• microbiome composition

  6 months after study start date

• impact of microbiome composition on length of hospitalization

  at the time of patient's discharge of the hospital

• Correlation between detected bacterial OTUs (Operation Taxonomic Units) and the event of reintervention

  90 days after surgery

• impact of microbiome metabolites on intestinal epithelial cell proliferation and wound healing

  6 months after study start date

Study Arms (1)

preoperative preparation on microbiome composition

Mechanical Bowel Preparation + oral antibiotics group: receiving mechanical bowel preparation only MBP will be prepared with 4 liters of Polyethylene glycol (PEG) solution to be started 24 hours before the planned surgery. 500mg of Metronidazole will be administrated 3 times one day before the surgery at 2 pm, 3 pm and 10 pm.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patient with rectal or left colon adenocarcinoma

You may qualify if:

• Adult ≥ 18 years old
• With histologically confirmed rectal or left colon adenocarcinoma by biopsy material from colonoscopy
• Having elective colorectal surgery after standardized bowel preparation
• Affiliated to a social security system
• Signature of informed consent

You may not qualify if:

• Major surgery 30 days before scheduled colorectal surgery
• Administration of systemic antibiotic therapy within 30 days prior to planned colorectal surgery
• Presenting a contraindication to elective colorectal surgery
• Patient protected by law
• Pregnant or breastfeeding woman

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Dr Lelde Lauka

Créteil, 94000, France

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

3 different microbiome samples will be taken from all patients. Two fresh fecal samples for detection of luminal microbiota (LM) and fecal water preparation: a) a day before the surgery before Mechanic Bowel Preparation (MBP) and/or antibiotics (ABT) (LM1), b) postoperatively after first bowel movement (LM2). One sample will be taken intra-operatively from the stapled resection lines of circular stapler used for forming a colorectal anastomosis, to detect the Mucosal Associated Microbiota (MAM) and to perform immunohistochemistry staining for detection of HACE1 expression.

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Colorectal Neoplasms; Postoperative Complications; Anastomotic Leak

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lelde Lauka, PHD

  APHP

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lelde Lauka, PHD

CONTACT

01 49 81 41 74; lelde.lauka@aphp.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2019
• First Posted: July 2, 2019
• Study Start: May 28, 2019
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: July 2, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)